ABSTRACT
Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Subject(s)
Humans , Paxillin/metabolism , Protein-Lysine 6-Oxidase/metabolism , Carcinoma, Squamous Cell/pathology , Epithelial-Mesenchymal Transition , Integrin alpha2beta1/metabolism , Mouth Neoplasms/pathology , Collagen/metabolism , Fibroblasts , Extracellular Vesicles/metabolism , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
Objective To investigate the effect of early screening and intervention on congenital hypothyroid-ism.Methods Thyroid stimulating hormone (TSH),three thyroid stimulating hormone (T3 )and thyroid hormone (T4 )were screened in 72h after birth,and thyroid ultrasound examination.All the patients were treated with the treat-ment of the left -to -thyroid hormone,0 -6 months medication dose 25 -50g/d,6 -12months medication dose 50 -100g/d,1 -3months medication dose 75 -100g/d.Serum TSH was reviewed every three months in the age of 1 years, 2 -3 years old every six months to review the serum TSH.Results The mean value of TSH in children with congeni-tal hypothyroidism was (68.7 ±15.3)mU /L.The mean value of T4 was (42.4 ±13.1)nmol/L.100 cases of chil-dren,including 38 cases of primary congenital hypothyroidism,transient congenital hypothyroidism in 62 cases.Ultra-sound examination showed primary congenital hypothyroidism were developmental abnormalities,and abnormal absence of a total of 18 cases (47.4%),Abnormal blood flow in 15 cases (39.5%);No abnormalities were found in the ultrasound examination of the transient congenital hypothyroidism.Before treatment,TSH in children with congenital hypothyroidism was significantly higher than that in the control group[(68.7 ±15.3)mU /L vs (4.6 ±1.1)mU /L], T4 was significantly lower than the control group[(42.4 ±13.1)nmol/L vs (124.4 ±45.5)nmol/L],the differences were statistically significant (t =22.867,16.058,all P 0.05).After 1 -3 years follow -up observation,children with Gesell development scale test showed that children with adaptability,large movements,fine movements,language and social skills to reach the normal level.Conclusion Early screening and treatment of the patients with congenital hypothyroidism is beneficial to the rehabilitation of the patients with congenital hypothyroidism.
ABSTRACT
Objective To investigate the effect of phenylephrine on the morphology and the expression level of Nampt mRNA in the irradiated osteoblasts of the rats,and to clarify the possible protective effects of phenylephrine on this injury.Methods The osteoblasts cultured by conventional tissue were randomly divided into control group, phenylephrine group,simple irradiation group,and phenylephrine+irradiation group.The cells in phenylephrine group were treated with 100 mmol· L-1 phenylephrine 30 min before irradiation.The cells in simple irradiation group were irradiated with 8 Gy X-ray.The osteoblasts were observed by microscope and were collected at the time points of 8,16,32 and 64 h after irradiation.The Nampt mRNA expression level in osteoblasts was examined by RT-PCR.Results There was no obviously morphological and number changes of osteoblasts in phenylephrine group compared with control group.The osteoblasts in simple irradiation group were atrophied,especially at 8 h;the number of osteoblasts in simple irradiation group was 0.82,0.37,0.24 and 0.21 times as control group respectively at 8,16,32 and 64 h. Atrophy of osteoblasts was alleviated in phenylephrine+irradiation group;at 8, 16,32 and 64 h,the number of osteoblasts was 0.91,0.83,0.72 and 0.75 times as control group,and was 1.09,2.24,3.00 and 3.60 times as simple irradiation group. The expression level of Nampt mRNA in the osteoblasts in simple irradiation group was reduced compared with control group (P < 0.01) at 8, 16, 32 and 64 h.There were significant differernces of the expression levels of Nampt mRNA in the osteoblasts between phenylephrine+irradiation group and control group (P < 0.01),and there were significant differernces between phenylephrine + irradiation group and simple irradiation group (P < 0.01 ) at the different time points. Conclusion Phenylephrine could reduce the atrophy of osteoblasts in the rats induced by irradiation and up-regulate the expression level of Nampt mRNA.Its protective effect on irradiated injury may be related to the up-regulation of the expression level of Nampt mRNA.
ABSTRACT
The paper introduces the ideas of designing hospital information system, including comprehensive cabling, network cover-age, ward calling system, ward monitoring system, queuing management, media teaching, multi -function hall, digital meeting and se-curity system, which would provide reference for the designing and implementation of hospital information system.